The energy metabolism of cardiac muscle is coupled to functional demands to that the myocardium mobilizes just enough energy to satisfy the work demand. The control mechanisms involved in the regulation of metabolism which bring about the necessary energy production are not clear. Adenylate charge, phosphorylation state and phosphorylcreatine charge have been suggested as candidates. It is the purpose of this investigation to elucidate the mechanisms involved in the regulation of metabolism which permit the necessary energy production during various levels of myocardial activity, and under conditions of metabolic disturbances. Cellular energy metabolism with particular emphasis on the controls of energy production will be studied in rat myocardial cells in monolayer cultures, as a model system, since the validity of any regulatory mechanism depends upon its relevance to the events in the living cell. The cell cultures will be subjected to normal physiologic conditions and to perturbations of energy metabolism, and specific energy reserves and possible metabolic regulators will be investigated. This investigation could pave the way to a better understanding of the mechanism of decreased mechanical performance of the myocardium under conditions of metabolic disturbances and to appropriate interventions.